Parathyroid hormone analogues for treatment of osteoporosis and hypercalcaemia

Abstract

Analogues of parathyroid hormone (PTH) and the parathyroid hormone-related peptide (PTHrP) have been proposed for the treatment of osteoporosis and hypercalcaemia of malignancy. The endocrine PTH regulates calcium homeostasis by its actions on bone, kidney, and intestinal receptors. If applied discontinuously, PTH has been shown to bring about an increase in bone mass in both animal models and small-scale human trials. The locally produced paracrine PTHrP is secreted in abundance by some tumours, resulting in severe hypercalcaemia. Numerous analogues of PTH, designed to have improved or more specific activities or to be more readily delivered, have been described in the patent literature as being possibly more effective than native PTH for osteoporosis treatment. Inactive analogues of PTHrP, which retain tight binding to the PTH/PTHrP receptor, have been proposed for the treatment of hypercalcaemia of malignancy. Related patent activities on the production of PTH by recombinant technologies and on the delivery of peptides by tracheal and oral routes are also discussed.

• hypercalcaemia
• osteoporosis
• parathyroid hormone